HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas

Feenstra, Manita; Veltkamp, Marcel; Kuik, J. van; Wiertsema, Selma P.; Slootweg, Pieter J.; Tweel, J Van Den; Weger, Roel de; Tilanus, Marcel G.J.

doi:10.1034/j.1399-0039.1999.540304.x

Cited by 89 publications

(87 citation statements)

References 34 publications

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“…Allelic loss at chromosome 6p was previously studied by seven STR markers (D6S473, D6S291, D6S273, D6S265, D6S105, D6S276, and D6S277) covering the chromosome 6p from centromere to telomere and correlated with HLA class I and TAP1 expression. Allelic loss was found with high frequencies and significantly correlated with down-regulated HLA class I and TAP1 expression (Fisher's exact test p ϭ 0.0196 and p ϭ 0.0464, respectively) (Feenstra et al, 1999b). However given the genomic distances between marker and HLA genes, allelic loss at a microsatellite marker may not necessarily reflect loss of HLA genes.…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory Investigation • March 2000 • Volume 80 • Number 3 (Feenstra et al, 1999b;Foulkes et al, 1993). In two (2 of 3) cases with normal HLA class I expression, allelic loss at 6p21.3 was identified with high density microsatellite analysis that was not identified by application of the 7 STRs used in our previous study.…”

Section: Genomic Loss Of Hla In Hnsccmentioning

confidence: 95%

“…One of these mechanisms, LOH of chromosome 6p, has been reported in various tumors of different origin (Foulkes et al, 1993;1999a;Randerson et al, 1996). Previously, we studied chromosomal deletions of the HLA region at 6p21.3 in head and neck squamous cell carcinomas using a limited panel of microsatellite markers (Feenstra et al, 1999b). LOH was studied using DNA isolated from ten 10 m cryostat sections containing at least 60% of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, 55 HNSCC were studied for LOH using seven microsatellite markers located on chromosome 6 and two markers flanking the ␤2m gene (Feenstra et al, 1999b). Most samples showed residual amplification of the lost allele in the tumor from co-isolated DNA derived from stromal cells.…”

Section: Loh Analysis On Microdissected Tumor Cellsmentioning

confidence: 99%

“…Recently, we reported a correlation of downregulation or loss of HLA class I expression in head and neck squamous cell carcinoma (HNSCC) and loss of heterozygosity (LOH) at 6p21.3 (Feenstra et al, 1999b). HLA class I, beta2-microglobulin (␤2m), and TAP expression was characterized by immunohistochemical procedures.…”

mentioning

confidence: 99%

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Microsatellite Analysis of Microdissected Tumor Cells and 6p High Density Microsatellite Analysis in Head and Neck Squamous Cell Carcinomas with Down-Regulated Human Leukocyte Antigen Class I Expression

Feenstra

Verdaasdonk

Zwan

et al. 2000

Laboratory Investigation

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SUMMARY: Down-regulated human leukocyte antigen (HLA) class I expression is frequently correlated with allelic loss at 6p21.3, which is the location of the HLA coding sequence, in head and neck squamous cell carcinomas (HNSCCs). Previously, we have demonstrated loss of heterozygosity (LOH) at 6p21.3 for at least one locus in 49% of the HNSCCs using 5 microsatellite markers spanning the 4 megabase HLA region. In the present study, the detection threshold (25%) to assign LOH was addressed by laser-assisted microdissection of tumor cells from tumors containing marginal loss. In addition, we describe high density microsatellite analysis of chromosome 6p21.3 in HNSCC with down-regulated HLA class I expression. The purpose of this study was to refine the identification of genetic alterations at 6p21.3 and to pinpoint allelic loss to individual HLA class I genes, using additional markers closely located to the HLA-A, -B, and -C loci and the transporter associated with antigen processing (TAP) genes. LOH analysis by amplification of microsatellite markers and subsequent fluorescent detection is a rapid and sensitive technique to predict HLA class I loss phenotypes in tumors. LOH can be identified at 25% relative signal reduction. Analysis of heterogeneous tumor samples and samples containing a small amount of tumor cells is facilitated by laser-assisted microdissection of tumor cells. In addition, we showed that accurate HLA LOH analysis requires application of microsatellite markers in close proximity to HLA class I and TAP genes. (Lab Invest 2000, 80:405-414).

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Section: Discussionmentioning

confidence: 99%

Section: Genomic Loss Of Hla In Hnsccmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Loh Analysis On Microdissected Tumor Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

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Microsatellite Analysis of Microdissected Tumor Cells and 6p High Density Microsatellite Analysis in Head and Neck Squamous Cell Carcinomas with Down-Regulated Human Leukocyte Antigen Class I Expression

Feenstra

Verdaasdonk

Zwan

et al. 2000

Laboratory Investigation

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Detection of a putativeHLA-A*31012 processed (intronless) pseudogene in a laryngeal squamous cell carcinoma

Feenstra¹,

Bakema²,

Verdaasdonk³

et al. 2000

Genes Chromosom. Cancer

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HLA class I and beta‐2‐microglobulin (β2m) expression in a moderately differentiated laryngeal squamous cell carcinoma appeared to be downregulated when analyzed by immunohistochemical procedures using the monomorphic anti‐HLA class I monoclonal antibody (mAb; W6/32), locus‐specific (HCA2 and HC10) and allele‐specific (LT129.11 and KRE501) mAbs and anti‐β2m mAbs. To reveal the molecular basis of downregulated HLA class I expression, HLA‐A typing was performed on DNA derived from peripheral blood lymphocytes (PBL) and the tumor. Sequencing‐based typing (SBT) revealed HLA‐A*02011, 31012. In addition to HLA‐A*02011, 31012 alleles, the tumor contained an HLA‐A*31012 allele, which lacked all introns when sequenced from the initiation codon through exon eight. The 3′ UTR region was intact up to at least 200 bp downstream. The mutant HLA‐A*31012 is restricted to laryngeal tumor tissue since it was not amplified in flanking tumor‐free laryngeal tissue. The mutant HLA‐A*31012 shares structural characteristics with processed pseudogenes, i.e., absence of introns and an intact 3′ UTR. This indicates that the mutant HLA‐A*31012 allele resulted from a retroposition (reverse transcription and integration) from the processed transcript of the wild‐type HLA‐A*31012 allele within a clonal tumor cell. Genes Chromosomes Cancer 27:26–34, 2000. © 2000 Wiley‐Liss, Inc.

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The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

Larson,

Doty,

Solheim

2024

Cancer Medicine

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Although the development of immunotherapies has been revolutionary in the treatment of several cancers, many cancer types remain unresponsive to immune‐based treatment and are largely managed by chemotherapy drugs. However, chemotherapeutics are not infallible and are frequently rendered ineffective as resistance develops from prolonged exposure. Recent investigations have indicated that some chemotherapy drugs have additional functions beyond their normative cytotoxic capacity and are in fact immune‐modifying agents. Of the pharmaceuticals with identified immune‐editing properties, gemcitabine is well‐studied and of interest to clinicians and scientists alike. Gemcitabine is a chemotherapy drug approved for the treatment of multiple cancers, including breast, lung, pancreatic, and ovarian. Because of its broad applications, relatively low toxicity profile, and history as a favorable combinatory partner, there is promise in the recharacterization of gemcitabine in the context of the immune system. Such efforts may allow the identification of suitable immunotherapeutic combinations, wherein gemcitabine can be used as a priming agent to improve immunotherapy efficacy in traditionally insensitive cancers. This review looks to highlight documented immunomodulatory abilities of one of the most well‐known chemotherapy agents, gemcitabine, relating to its influence on cells and proteins of the immune system.

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HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas

Cited by 89 publications

References 34 publications

Microsatellite Analysis of Microdissected Tumor Cells and 6p High Density Microsatellite Analysis in Head and Neck Squamous Cell Carcinomas with Down-Regulated Human Leukocyte Antigen Class I Expression

Microsatellite Analysis of Microdissected Tumor Cells and 6p High Density Microsatellite Analysis in Head and Neck Squamous Cell Carcinomas with Down-Regulated Human Leukocyte Antigen Class I Expression

Detection of a putativeHLA-A*31012 processed (intronless) pseudogene in a laryngeal squamous cell carcinoma

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

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